A pharmacokinetic study of stable isotopically labeled phenobarbital in epileptic patients was carried out. Plasma concentration-time profiles of the stable isotopically labeled phenobarbital were monitored by GCMS computer system. The pharmacokinetics of phenobarbital were determined at a time when the patient was in steady-state in terms of unlabeled phenobarbital. Labeled phenobarbital could be quantitated to 0.3 micrograms/ml when the labeled phenobarbital plasma levels were 90 micrograms/ml. The pharmacokinetic parameters were: kel equals 0.0055/hr, t1/2 equals 126 hr, VD equals 34.3 liters and total clearance equals 189 ml/hr. These data will be used as control values and compared to those obtained when phenobarbital is given with valproic acid in an effort to determine the mechanisms for this drug-drug interaction.